15. Leukocyte Disorders Flashcards
1
Q
Quantitative vs. Qualitative WBC Examination
A
Quantitative: Leukocytosis, leukopenia; Absolute vs. relative
Qualitative changes: Nuclear, Cytoplasmic
2
Q
Neutrophil Number is affected by:
A
- Influx - production and release from bone marrow
- Circulating vs. marginal
- Exit from blood - as circulating become marginal, there is a drop in Neutrophil count
3
Q
Leukocytosis
- physiologic
- pathologic
- responses (lab findings)
- factors determining host response
A
Physiologic:
- Causes a distribution change (increase in circulating, decrease in marginal)
- due to Severe exercise, Stress, fear, anger, or Hypoxia
Pathologic:
- Infection -Toxins, (uremia, spider bite, Pb poisoning)
- Tissue necrosis (MI, burns)
- Malignant neoplasm
- Hemorrhage, especially in gut
- Acute hemolysis
Response to infection - Increased WBC - higher WBC indicates good response - Left Shift - Decreases eosinophils Recovery from infection - Decrease neutrophils - Increase monos - Increase lymphs, eos
Factors determining host response: Age, Nutritional status, Kind of invading organism
4
Q
Morphologic of Neutrophils in infection
A
- Toxic granulation - immature azurophilic granules due to rapid WBC production
- Dohle bodies - Cytoplasmic, residual RNA
- Cytoplasmic vacuoles - phagocytosis
- Nuclear spicules - found in some infections
5
Q
Neutropenia
A
- Decrease entry into blood (production)
- can be caused by:
- Viral infection, Inherited - infants, Drugs, Ineffective granulopoieses
- Increase removal from blood (destruction): Severe uncompensated infection, Hypersplenism, Antibodies (leukoagglutinins)
- Circulating and marginal pool alterations
6
Q
Chronic Granulomatous Disease
A
- Sex-linked or autosomal recessive
- 1/500,000
- Recurrent bacterial or fungal infections
- Most often seen in the pediatric population
- Treatment is prophylactic antibiotics, early treatment of infections
- Neutrophils appear normal, but have abnormal function
- Organisms are phagocytized, but not killed
- Defects in the respiratory burst system
- Reduced superoxide production
7
Q
Nitroblue Tetrazolium Test
A
- Neutrophils are mixed with a yellow dye (NBT] and microorganisms
- Normal: dye is reduced by the generation of oxygen metabolites to blue
- CGD: dye is not reduced because of inability to generate a respiratory burst (can engulf but can’t break things down)
8
Q
Chediak-Higashi Syndrome
A
- Rare autosomal recessive disorder
- Death usually occurs in infancy or childhood
- Giant granules formed by aggregation and fusion of primary and specific granules (seen in most granule-containing cells)
- Prevents delivery of granules to phagosomes
- Lab Values: neutropenia, thrombocytopenia
- Patient Presentation: Skin hypopigmentation, Silvery hair, Photophobia (abnormal melanosomes), Lymphadenopathy and hepatosplenomegaly
9
Q
May-Hegglin Anomaly
A
- Rare, autosomal dominant trait
- Dohle-like inclusions in granulocytes: consist mainly on RNA from rough endoplasmic reticulum
- Giant platelets
- Variable thrombocytopenia
- Only clinical problem is bleeding due to thrombocytopenia, if present
10
Q
Alder-Reilly Anomaly
A
- Characterized by the presence of large purplish granules in all leukocytes
- Cells function normally
- Associated with mucopolysaccharidosis such as Hurler’s syndrome and Hunter’s syndrome
11
Q
Pelger-Huet Anomaly
A
- Benign, autosomal dominant
- 1/5000
- Neutrophil hyposegmentation
- Neutrophil nucleus does not segment beyond two lobes
- Nuclear clumping intense
- Dumbbell, pince-nez
- Yet, neutrophils still function normally
12
Q
Acquired or pseudo Pelger-Huet
A
- seen in myeloproliferative disorders or myelodysplastic states
- frequently accompanied by hypogranulation
13
Q
Morphology of Monocytes
A
- Spectrum of mononuclear phagocytic cells
- Small (14 - 20u) to large (20 - 30u)
- Nucleus: Reniform, fine chromatin, no nucleolus
- Cytoplasm: Gray-blue, contains fine lysosomal granules; Vacuoles, particularly when sample sits
- Numerous small mitochondria in gray cytoplasm
- Complex golgi zone - produces granules
- Lysosomal granules
- Move by undulating pseudopods
14
Q
Monocyte - Macrophage Transformation
A
Bone Marrow = Monoblast, Promonoblast
Blood = Monocyte
Tissue = Macrophage
- Enlargement (25 - 50u)
- Increased energy production and consumption
- Azurophilic granules disappear, new enzymes synthesized
- Active phagocytosis, pinocytosis
- Respond to chemotaxis
15
Q
Macrophage Function
A
- Interferon production: prevent viral spread
- Antibody response: Trap antigen, “process antigen”, cell-mediated immunity
- Wound healing: stimulate fibroblast formation
- Granulocyte and monocyte regulation: Colony stimulating factor
16
Q
Macrophage Types
A
- Fixed (sessile)
- Wandering (motile)
- Peritoneal
- Liver (Kupffer cells)
- Alveolar (lung)
- Splenic
- Osteoclasts (bone resorption)
17
Q
Monocytosis
A
- Absolute: >1000/uL
- Relative: >10%
- Causes:
- recovery from acute bacterial infection
- Other infections (TB*, SBE, syphilis, some viral)
- Protozoal and rickettsial infection - malaria, typhus, Rocky Mountain spotted fever
- Malignancy
- Hematologic disease (over 1/2): Leukemia, lymphoma, myeloproliferative disorders, multiple myeloma, lipid storage disease
- Collagen, vascular disease: SLE, rheumatoid arthritis
- “Preleukemia” - precedes leukemia
- Poisoning - rare (ex. tetrachloroethane)
18
Q
Lipid Storage Diseases
A
- Gaucher’s Disease
- Niemann-Pick Disease
- Tay-Sachs Disease
19
Q
Gaucher’s Disease
A
- lipid storage disease
- Autosomal recessive, lipid storage disease
- Type I more common in Ashkenazi Jews
- *** Lack of Beta-glucocerebrosidase
- Unable to digest the stroma of ingested cells
- Lipid accumulates in macrophages (Gaucher cells)
20
Q
Gaucher cells
A
- Large cells with small, eccentric nuclei
- Fibrillar (onion skin-like) cytoplasm
- Cells often filled with debris
- Cells found in lymphoid tissue, spleen, liver, and bone marrow (not blood)
21
Q
Niemann-Pick Disease
A
- Autosomal Recessive, most commonly seen in Ashkenazi Jews
- Shingomyelinase Deficiency
- Sphingomyelin and cholesterol accumulate in macrophages
- Foamy macrophages found in lymphoid tissue and bone marrow
- Most common (85%) have onset in infancy
- Failure to thrive
- Retarded mental and physical development
- Hepatosplenomegaly
- Half with cherry-red spot in macula of eye
- Prognosis is poor; few survive beyond third birthday
22
Q
Normal Lymphocyte
A
- Infants - 90% of cells are lymphs (because they still have to build their immunity)
- Adults - about 1/3 are lymphs
- T-cell count is highest at birth
23
Q
Lymphocytosis in the Blood
A
- Increased lymphocyte count
- Absolute Lymphocytosis ( >9 x 10^9/L (child), >4 x 10^9/L (adult))
- Relative Lymphocytosis (>70% (child), >45% (adult))
24
Q
Lymphocytopenia in the Blood
A
- Decreased lymphocyte count
- Absolute Lymphocytopenia (<20% (adult))
25
Q
DiGeorge Syndrome
A
- T-cell abnormality
- Underdeveloped thymus
- Markedly decreased T lymphocytes
- May have neurologic, cardiac, parathyroid complications
- Treatment with thymus transplant
26
Q
Combined T and B Lymphocyte Abnormalities
A
- Severe Combined Immunodeficiency (SCID): Results in severely decreased T, B, and natural killer lymphocytes
- Wiskott-Aldrich syndrome:
- Deficiency of protein required for migration, adhesion and activation of WBC
- Causes immunodeficiency, eczema, and thrombocytopenia
27
Q
Infectious Mononucleosis:
- who it commonly effects
- caused by:
- transmitted by:
A
- Dr. M.A. Epstein, 1964
- Young adults, rarely over 24 years old
- Caused by the Epstein-Barr Virus
- EBV is a herpes virus
- Transmitted by: Oral contact (“kissing disease”), Fomites (toothbrush, drinking glass), Transfusions
- Over 200,000 cases per year
- Peak incidence ages 17 - 25
- 95% of adults between 35 & 45 have been infected
- Incubation 2- 4 weeks
28
Q
Infectious Mononucleosis:
- symptoms
- laboratory findings
A
- Triad of Symptoms: Fever, Lymphadenopathy, Sore Throat
- Leukocytosis due to lymphocytosis
- Atypical/reactive lymphocytes >10%
- Serologic testing
*Note: MONOnucleosis does not involve monocytes. It involves reactive lymphocytes
